Patient Education


brother sitting in chair holding baby, photographer Sathyatripodi
Women can help to promote a healthy pregnancy and birth of a healthy infant by taking the following steps before they become pregnant1:
  • empty baby shoes in between adult shoesDevelop a plan for their reproductive life. Almost half of all pregnancies are unintended, so preparation for pregnancy may be inadequate. Increase their daily intake of folic acid (one of the B vitamins) to at least 400 micrograms. Taking 400 micrograms of folic acid daily reduces the risk for neural tube defects (spina bifida) by 70%.4 Most prenatal vitamins contain the recommended 400 micrograms of folic acid as well as other vitamins that pregnant women and their developing fetus need.1,5 Folic acid has been added to foods like cereals, breads and pasta. Folate, present in fruits and vegetables, is not as well absorbed as folic acid.
  • Make sure their immunizations are up to date. It is safe to take flu shots as well as diphtheria, tetanus and pertussis (Tdap) vaccines during pregnancy. These reduce illness and pregnancy complications.
  • Control diabetes and other medical conditions. Poorly controlled diabetes increases the risk of birth defects, as well as increasing the likelihood of obesity in the child.
  • outdoor group exercise class
  • Avoid smoking, drinking alcohol, and using drugs. Tobacco smoke and alcohol use during pregnancy have been shown to increase the risk for Sudden Infant Death Syndrome. Alcohol use also increases the risk for fetal alcohol spectrum disorders, which can cause a variety of problems such as abnormal facial features, having a small head, poor coordination, poor memory, intellectual disability, and problems with the heart, kidneys, or bones.2 According to one recent study supported by the NIH, these and other long-term problems can occur even with low levels of prenatal alcohol exposure.3
  • Attain a healthy weight. Obesity causes maternal complications as well as increasing the likelihood of childhood obesity and diabetes.
  • Learn about their family health history and that of their partner. Genetic testing is available for a ever increasing number of genetic diseases. There are now ways to smiling couple laying on grassprevent these illnesses from affecting the next generation.
  • Seek help for depression or anxiety. Psychotherapy and many psychiatric medications are safe during pregnancy, and untreated depression has a worse outcome.



Preconception and prenatal care can help prevent complications and inform women about important steps they can take to protect their infant and ensure a healthy pregnancy. With regular prenatal care women can:

  • Reduce the risk of pregnancy complications. Following a healthy, safe diet; getting regular exercise; and avoiding exposure to potentially harmful substances such as lead and radiation can help reduce the risk for problems during pregnancy and ensure the infant's health and development. Controlling existing conditions, such as high blood pressure and diabetes, is important to avoid serious complications in pregnancy such as preeclampsia.
  • Help ensure the medications women take are safe. Certain medications, including some acne treatments6 and dietary and herbal supplements7, are not safe to take during pregnancy.


References
  1. Preconception Care Work Group and the Select Panel on Preconception Care. Centers for Disease Control and Prevention. (2006). A report of the CDC/ATSDR

  2. Fetal alcohol spectrum disorders. Centers for Disease Control and Prevention. (2011)

  3. Persistent dose-dependent changes in brain structure in young adults with low-to-moderate alcohol exposure in utero. Eckstrand, K. L., Ding, Z., Dodge, N. C., Cowan, R. L., Jacobson, J. L., Jacobson, S. W., et al. (2012). Alcoholism: Clinical and Experimental Research, 36(11), 1892-1902. PMID: 22594302

  4. National Center on Birth Defects and Developmental Disabilities Strategic Plan 2011–2015. PDF download Centers for Disease Control and Prevention. (2011).

  5. Dietary supplements fact sheet: Folate. NIH Office of Dietary Supplements. (2009)
  6.  
  7. Acne treatment during pregnancy. American Pregnancy Association. (2007)
  8.  
  9. Prenatal care fact sheet. Department of Health and Human Services. (2009)

back to top

Dealing with infertility is intimidating for many people. Less than 50 percent of couples who are referred to an infertility specialist end up making an appointment. They’re afraid their problem can’t be treated or that the cost will be too high. But evaluation by a caring physician may uncover simple causes that allow many patients to conceive on their own.


couple sitting in sunset


How to know if you're infertile

The formal definition of infertility is failure to conceive after one year of trying to become pregnant. Conception usually takes place within 6 months of trying, so if you're having sex at the "right" time (within 2-3 days of ovulation), then it's time to look at causes. If travel, illness, or stress is preventing you and your partner from having sex, then a frank discussion of lifestyle may help identify stress and ways to improve chances for spontaneous pregnancy.

The initial infertility evaluation should involve a physical exam, focusing on signs or symptoms of anovulation, hormonal imbalance or pain. If not previously done, documentation of ovulation with temperature charts or over-the-counter ovulation predictor kits can be reassuring. These tests also help verify that sex is happening at the right time of the month.

Other diagnostic tests can help establish the cause of infertility. These tests typically include evaluation of the husband (semen analysis), the fallopian tubes (hysterosalpingogram or HSG), hormonal assessments (blood tests) or even laparoscopy to rule out endometriosis.

Basic Treatment

Sometimes treatment will be recommended, even if there's no real cause identified. Clomiphene citrate (Clomid or Serophene) or Letrozole (Femara), tablets will enhance or establish ovulation. 10-15% of women may conceive with this treatment. There are concerns about use of Clomiphene for an extended period of time, as there is an increased risk of breast cancer in women using this medication for more than 12 months. (1)

When to see a Specialist

If pregnancy doesn’t occur after 3-6 months of simple treatment, the next step is seeing a Reproductive Endocrinologist (RE) who specializes in the evaluation and treatment of infertility. Seeing a specialist in a timely fashion is important, since the likelihood of conceiving goes down as women and men age.

Is Stress Causing Infertility?

Once a patient comes to see a RE the first step will be to review prior testing. Further diagnostic testing may be required, but often taking a step back to look at the patient’s environment is more important. Too often, physicians fail to recognize the interaction between hormones, nutrition, stress and genetics.

Both men and women can develop stress induced reproductive compromise and infertility. In men, reduced hypothalamic-gonadal function (how the brain controls hormones) may result in abnormal sperm counts and no other symptoms, or can cause decreased libido, loss of muscle mass and fatigue.

Chronic stress causes abnormal activation of the adrenal system, with increased levels of the stress hormone cortisol. These interfere with normal function of the hypothalamic-pituitary-gonadal axis, which signals the ovaries or testes to produce eggs or sperm and normal hormones. The stressors may be nutritional, metabolic or psychogenic. Stress is definitely a cause of reduced fertility. Stress can affect a couples ability to have sex at the “right time”, and even prevent ovulation or implantation. We all know people who seem to thrive on stress, but most of us will be affected by stress in subtle or obvious ways.

Stress induced reproductive compromise is all too often ignored during the infertility evaluation, often with the assumption that fertility treatment can reverse the problem without dealing with the underlying issues. Potent fertility drugs and in vitro fertilization may induce ovulation, allowing pregnancy to occur. However, ignoring the underlying causes of infertility may lead to increased side effects from medications, and higher risks of prematurity or birth defects. Taking time for a thorough evaluation and appropriate treatment of metabolic (energetic/nutritional), or psychogenic (emotional, such as with depression, anxiety, PTSD, etc.) problems increases the likelihood of a healthy pregnancy and baby.

Since stress is so common in patients with infertility, even when stress is not the primary cause of infertility, it makes sense that better outcomes can be expected when stress reduction is a part of the pretreatment plan. Once psychosocial/metabolic/stress issues have been addressed, and a diagnosis has been established, directed therapy can be implemented. For example, if the woman is not ovulating, ovulation induction will be necessary. If the man has low sperm concentrations, intrauterine insemination with sperm preparation to concentrate the healthy sperm may be used.

Blausen medical illustration of intrauterine insemination

Intrauterine Insemination - Blausen.com staff

Outcomes

The medical literature shows that fertility therapy is reasonably efficient, with most couple becoming pregnant within 4-6 cycles of a given treatment. Some patients may take longer to conceive, or may have to resort to high tech treatment, such as IVF. Reassessment and possible change of therapy is indicated if a healthy conception is not reached within a reasonable time frame, but these decisions are often based on emotional, financial and religious/ethical considerations of the individual patient.

In some cases, all testing is normal and we cannot find the "reason" for the couple's infertility. This is the case about 15% of the time. These couples are thought to have “unexplained” or Idiopathic Infertility. This diagnosis can be very difficult emotionally because couples are frustrated when a problem cannot be identified. Clearly there is a problem preventing pregnancy; however we may not have the tools yet to identify what it is. Even though this may be an emotionally difficult diagnosis to deal with, the good news is that couples with unexplained infertility have an excellent prognosis for success with treatment.

Next steps

Unfortunately some couples will not get pregnant with simple therapy, such as lifestyle/stress management, fertility medication, acupuncture, or intrauterine insemination. Usually the next step for infertility treatment is In Vitro Fertilization (IVF). This involves removing eggs from the ovaries, and bypassing the fallopian tubes by mixing the eggs with sperm in a petri dish. Once embryo development is documented, an embryo is placed directly into the uterus, and then hopefully normal implantation and pregnancy will occur.

Blausen medical illustration of In Vitro Fertilization

In Vitro Fertilization - Blausen.com staff


IVF is a very powerful tool in that it bypasses non-functioning tubes. It may minimize the impact of endometriosis, and it can bypass male factors, allowing men with very low sperm counts to father a child. While IVF can solve many problems that prevent pregnancy, there is still an increased risk of multiple birth, as well as more difficult deliveries (2), and lower birth weight in babies born as a result of IVF. Recent studies have indicated a slightly higher risk of birth defects in babies conceived from IVF. (3)

Effect of Age on Fertility

We know that all women have a "biological clock." The difficult part is to determine when a given woman has undergone the transition from having "good" eggs to "bad" eggs. We know that typically this will happen in the decade between ages 35 and 45 but it can actually happen at any time. Ovarian “reserve” testing to assess the lifecycle of the ovaries should be an integral part of an infertility evaluation.

Unfortunately, a woman may not have any symptoms that her eggs quality is decreasing. By the time symptoms such as irregular cycles, hot flashes etc. appear, it may be too late. If a woman has abnormal egg quality (usually referred to as "abnormal ovarian reserve") then treatment is usually much more aggressive, and success rates may be low (as low as a 10-20% chance of a pregnancy occurring, but with an increased risk of miscarriage as well). Treatment may not improve outcome, depending on other fertility factors, so a prompt evaluation is important to determine if there is any benefit of treatment.

Other Options if Fertility Treatment Doesn’t Work

Infertility is a loss. The couple will find that they are unable to have that which comes naturally to others. Grieving this loss is an important part of moving on. It may take months or longer to process grief and adapt to childlessness. (4) Unfortunately, miscarriage occurs in 10-15% of pregnancies, which may make the grieving process worse. A study of women who miscarried after infertility therapy found patients had a variety of responses: a sense of profound loss and grief; diminished control; a sense of shared loss with their partners; injustice or lack of fairness; ongoing reminders of the loss; social awkwardness; fear of re-investing in the treatment process or a subsequent pregnancy; the need to make sense of their experience; and feelings of personal responsibility for what had happened. Clearly, processing and healing from the experience is necessary before moving back into treatment. (5)

Once patients have grieved, processed, and reached resolution, different choices will be available. Adoption is the right choice for some patients. If the lack of success is due to poor quality eggs, donor eggs have enabled many couples to be parents. Other patients may choose to remain childless, deciding to find family in different ways, whether it be with adult relationships, or including friends and family with children in their lives. Regardless of the outcome, fertility treatment is stressful, and there may be long term outcomes that are frequently not considered, such as ongoing depression (6) and potential long term effects of fertility medication treatment.

With infertility, sometimes the process is as important as the outcome. Of course every patient hopes to have a healthy baby, but no matter the outcome, what’s important is to be able to look back and be at peace with your decisions.


couple looking at water
References
  1. Breast cancer incidence after hormonal treatments for infertility: systematic review and meta-analysis of population-based studies. Gennari A, Costa M, Puntoni M, Paleari L, De Censi A, Sormani MP, Provinciali N, Bruzzi P.

  2. The Risk of Major Birth Defects after Intracytoplasmic Sperm Injection and in Vitro Fertilization. Michèle Hansen, M.P.H., Jennifer J. Kurinczuk, M.D., Carol Bower, M.B., B.S., Ph.D., and Sandra Webb, Ph.D.

  3. Is there an association between assisted reproductive technologies and time and complications of the third stage of labor? Aziz MM, Guirguis G, Maratto S, Benito C, Forman EJ.

  4. Unresolved grief in women and men in Sweden three years after undergoing unsuccessful in vitro fertilization treatment. Volgsten H1, Svanberg AS, Olsson P.

  5. The experience of spontaneous pregnancy loss for infertile women who have conceived through assisted reproduction technology. Harris DL, Daniluk JC.

  6. Mental health in women 20-23 years after IVF treatment: a Swedish cross- sectional study. Vikström J, Josefsson A, Bladh M, Sydsjö G.


back to top
Integrative, or “mind-body” therapies are defined as complementary and alternative therapies used to address the “ways in which emotional, mental, social, spiritual, experiential, and behavioral factors can directly affect health.” The understanding is that the brain interacts with the rest of the body, impacting our physical health – including fertility.

couple sitting lakeside, she's about to kiss him

Stress levels are powerful. Chronic stress can run the body down causing normally functioning systems of the body to “shut down” (even if temporarily) so that the vital functions of the body – heart, lungs and nervous system – can maintain function to keep us alive. Since the reproductive system is not necessarily vital to keep us alive, it shuts down if there is excessive stress. It is well known that girls stop having menstrual periods during intense periods of mental or physical stress. Pregnancy and lactation require huge amounts of energy to be successful. If stress is severe enough, then survival requires a shift of energy away from reproduction.

Research has shown that stress impacts fertility by causing high levels of stress hormones such as adrenaline, catecholamines and cortisol. These can inhibit the release of the body’s “master” reproductive hormone, GnRH (gonadotropin releasing hormone), which is produced by the Hypothalamus. GnRH is responsible for the release of the sex hormones, LH and FSH. LH and FSH stimulate the gonads (ovaries in women, testes in men) to produce gametes (eggs and sperm) and sex hormones (estrogens and androgens). When GnRH is suppressed by stress, tumors, or medications, this leads to suppression of normal ovulation in women, sperm count in men and sexual activity and hormone balance in both women and men. Infertility definitely causes varying levels of stress, but stress from our daily lives – work, a commute, an overbooked schedule, managing a home and the demands of family – also impact our levels of stress. It is important to create a stress reduction plan for yourself that includes mind and body therapies, as well as a few small indulgences, that you can use at a moment’s notice and in any stressful situation.

People living with high stress levels often choose poor dietary and lifestyle habits. It is critical to maintain good nutrition and avoid smoking, drugs and alcohol use in the months leading to conception. A healthy diet goes a long way toward improving fertility, with higher pregnancy rates in women who eat poly- and mono-unsaturated fats, high quality carbohydrates, fruits and vegetables, and lean meats and fish. High intake of Omega-3 fish oils are beneficial, and have beneficial effects on uterine blood flow.

Chronic stress may cause lack of libido as well as a decrease in general fertility. Having sex on a schedule can be very stressful, and sometimes sex becomes impossible. Men can have erectile dysfunction due to performance anxiety. Sometimes behavior modification with stress relief can cure the problem, and natural conception can occur.

variety of colorful fresh produce

It is important to consider stress levels if you have been trying to conceive with no results. Stress may cause subtle effects on ovulation and implantation due to abnormal hormone levels. Stress relief should be a part of every couple’s conception plan regardless of whether they are trying to conceive naturally, or going through fertility treatment.


Reducing Stress for Fertility
home pregnancy test

In you are having difficulty conceiving, stress may very well be a factor. If you have had fertility tests performed and have found that there is no medical reason for your infertility, it is time to evaluate your life and determine how much stress you have. Of course, you may not even have need for an evaluation. You may know you are stressed. In that case, it is time to start defeating that stress to help your fertility.

1. Reduce the stress in your life.

This of course if obvious, as well as easier said than done. Reducing the stress in your life is so important on many different levels. It will not only help your fertility and health but also your quality of life. If your job is really stressful, maybe begin to look for a different job or occupation. If that is not possible, some of the tips below will help you to deal with your stress differently than how you currently are.

2. Change how you react to stressful situations.

When faced with an ongoing stressful situation there is only one thing you have control over… how you react. Pay attention to how you react to the stressful people at work, or to your stressful situation. Do you turn it over in your head all night long, do you create scary future visions of what could happen? Getting control of how you react will have a big impact on what happens inside of your body when a stressful situation presents itself. This takes some attention and practice.

3. Have a practice or habit that helps you to reduce stress.

Here are some suggestions of practices or daily habits that help reduce the effects of stress on your health.

  • Make sure you are getting enough sleep
  • Get an adequate amount of healthy exercise daily
  • Meditate
  • Start practicing Yoga
  • Seek counseling
  • Consume caffeine free tea, such as chamomile
  • Use bee pollen, lemon balm, and maca root
  • Acupuncture
  • Prayer
  • Read a book in the park
  • Journal
  • Take warm baths
  • Surrender and let go
  • Fertility Meditation
man and woman practicing yoga mediatation
4. Three Books that may help transform stress.

These books may help you find new ways in how you react to stressful situations.

back to top

Chronic stress may cause hormonal imbalance, lowered egg and sperm health, as well as create a lack of libido. Herbs that support a healthy stress response, nourish the nervous system and support endocrine function are good choices for women who are trying to conceive, or just want to be healthier.

Ashwagandha root (Withania somnifera)

Both a nervine and adaptogen, Ashwagandha works to re-regulate thyroid and adrenal gland function, as well as support overall endocrine system function for improved stress response and hormonal balance.

Adaptogens are substances (a combination of amino acids, vitamins, and herbs) that modulate your response to stress or a changing environment. Adaptogens help the body cope with external stresses such as toxins in the environment and internal stresses such as anxiety and insomnia. Medical researchers have been studying Ashwagandha for years with great interest and have completed more than 200 studies on the healing benefits of this botanical. More on ashwaganda…

Bee Pollen/Propolis

Bee pollen has been reported to have great results in boosting immunity and fertility. Bee propolis has been found to support healthy immune function, inflammation and stress response in the body.

Humans have been using this as an antiseptic since the times of ancient Egypt. Applying propolis to wounds greatly improved healing and throughout the centuries, this substance has been shown to have other healing properties as well. In the last several decades, health practitioners have found even more positive uses for propolis as a natural supplement. Propolis has been shown to increase the effects of other antibiotics like penicillin and can also strengthen the immune system. Studies are now being done to see if propolis can become an effective treatment for the prevention of certain types of cancer. More on bee pollen/propolis…

Chamomile flowers (Matricaria recutita)
chamomile flowers, photographer szjeno09190

This herb is a nervine and mild sedative which may help to reduce stress, relax the nervous system and induce a restful state in the body.

Chamomile is an age-old medicinal herb known in ancient Egypt, Greece and Rome. Chamomile's popularity grew throughout the Middle Ages when people turned to it as a remedy for numerous medical complaints including asthma, colic, fevers, inflammations, nausea, nervous complaints, children's ailments, skin diseases and cancer. As a popular remedy, it may be thought of as the European counterpart of the Chinese tonic Ginseng.

Eleuthero root and stem bark (Eleutherococcus senticosus)

Also known as Siberian Ginseng, Eleuthero root/bark strengthens the immune system and is great for people under severe stress. This herb helps people to feel better, perform better and recover from immune suppression more quickly.

Eleuthero has been used in China for 2000 years as a folk remedy for bronchitis, heart ailments, and rheumatism, and as a tonic to restore vigor, improve general health, restore memory, promote healthy appetite, and increase stamina. Referred to as ci wu ju in Chinese medicine, it was used to prevent respiratory tract infections as well as colds and flu. It was also believed to provide energy and vitality. In Russia, eleuthero was originally used by people in the Taiga region of Siberia to increase performance and quality of life and to decrease infections.

Fo-ti also known as Ho Shou Wu, root (Polygonum multiflorum)

According to TCM, Fo-ti root helps to restore jing (life essence). It has also been found to be supportive of both thyroid and adrenal function, which are highly sensitive to stress and are extremely important to fertility health. The vine and leaf are sometimes used to aid stress, nervous tension and insomnia.

Modern research indicates that this herb contains an alkaloid that has rejuvenating effects on the nerves, brain cells and endocrine glands. It stimulates a portion of the adrenal gland and helps to detoxify the body. It has been used for a long list of ailments including atherosclerosis, constipation, fatigue, high cholesterol, high blood pressure, blood deficiency, nerve damage, eczema, scrofula and inflammation of lymph nodes and heat toxicity. It is also indicated to boost the immune system and increase sexual vigor. More on fo-ti root…

fo-ti (polygonum-multiflorum) pieces of dried root
Lemon Balm leaf (Melissa officinalis)

Lemon Balm provides excellent nervous system support. It supports a healthy stress response, lessens depression and anxiety. Good emotional health, and stress response is important prior to conception. This herb is not intended for use in people dealing with hypothyroidism.

Linden flower and bract (Tilia platyphyllos, T.cordata)
branch of flowers on linden tree, photographer szjeno09190

This herb mildly lowers blood pressure, reduces depression and supports nervous system function. It is great for anxiety, depression and insomnia, and is considered very gentle and safe.

It appears to have antispasmodic (reducing muscle contractions), astringent (drying), diuretic, and sedative properties. Tilia flowers are sometimes suggested to treat colds, cough, fever, infections, inflammation, high blood pressure, headache (particularly migraine); as a diuretic (increases urine production), antispasmodic (reduces smooth muscle spasm along the digestive tract), and sedative. Tilia wood is used for liver and gallbladder disorders and cellulitis (inflammation of the skin and surrounding soft tissue). Tilia charcoal has been used orally to treat intestinal disorders.

Maca root (Lepidium meyenii)

Maca is a nourishing food for the endocrine system, aiding the pituitary, adrenal, and thyroid glands (all involved in hormonal balance.) It is also supportive of both immune and stress responses in the body. More on maca root…

Motherwort aerial parts (Leonurus cardiaca)

Famous herbalist Nicholas Culpepper (1616-1654) said, “There is no better herb to drive away melancholy vapours from the heart, to strengthen it and make the mind cheerful.” Motherwort supports heart health and aids in the reduction of anxiety. More on motherwort…

Schisandra fruit and seed (Schisandra chinensis)

Schisandra acts as an adaptogen, as well as supports healthy hormonal balance through endocrine system support. Additionally, it promotes proper immune and stress responses.

Schisandra chinensis enjoys millennia of traditional use for prolong life, retarding the aging process, increasing energy, as a fatigue-fighter, and as a sexual tonic. Schisandra also possesses significant protective antioxidant and anti-inflammatory activity. Thus it helps to maintain healthy cells throughout the body. It is considered one of the most highly protective of all medicinal plants, and the berry is included in many traditional herbal formulas for improving energy and mental health.

“Schisandra chinensis owes its name wu wei zi (five-flavored berry) to the fact that it is sweet, sour, salty, bitter and pungent.” - Chris Kilham, The Dr. Oz Show

Shatavari root (Asparagus racemosus)

Not only does this herb support healthy fertility, it is an immune system and nutritive tonic. Shatavari also supports overall immune system function. More on shatavari root…


back to top

There are numerous studies, some in animal models, and some in humans. Sometimes there’s disagreement. These vitamins have been associated with lower risk of miscarriage. Discuss these findings with your doctor before starting any supplements. Remember, whole food is the best way to get vitamins (except Vitamin D). Vegans do need to take extra B vitamins, especially B12.



Dietary Fat and Fertility
olive oil being poured into small bowl
Increasing monounsaturated fat in diet improves fertility

In a study of some 17,000 women conducted by the Harvard School of Public Health, researchers were able to define a group of "fertility foods" able to improve odds. Eating more monounsaturated fats (like olive oil) and less trans fats (like the kind found in many baked goods or fast foods) was one of the keys to increasing fertility. More on ways to encourage fertility…

squares of chocolate
Eating chocolate daily lowers miscarriage risk by 19%

The aim of this study was to examine the association between biological, behavioural and lifestyle risk factors and risk of miscarriage. Six hundred and three women aged 18–55 years whose most recent pregnancy had ended in first trimester miscarriage (<13 weeks of gestation; cases) and 6116 women aged 18–55 year whose most recent pregnancy had progressed beyond 12 weeks (controls) were questioned about socio-­‐demographic, behavioural and other factors in their most recent pregnancy. Consumption of chocolate daily or on most days was associated with reduced odds of miscarriage (odds ratio = 0.81). Not a huge benefit, but just another reason to eat chocolate! More on chocolate consumption and miscarriage…



Vitamins and Miscarriage
Folate status in young overweight and obese women

Changes associated with weight reduction and increased folate intake. J Nutr Sci Vitaminol (Tokyo). 2009 Apr;55(2):149‐55. Ortega RM, López‐Sobaler AM, Andrés P, Rodríguez‐Rodríguez E, Aparicio A, Perea JM. Obesity lowers folate status, despite similar dietary intake; weight loss increases folate status.

Low folate status

Low folate status associated with 47% higher risk of miscarriage, may cause abnormal karyotype. Lena George, M.D., et al. Plasma Folate Levels and Risk of Spontaneous Abortion. Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL, women with low (< or =2.19 ng/mL) folate levels were at increased risk of miscarriage (adjusted odds ratio, 1.47), whereas women with higher folate levels (3.96-­‐6.16 ng/mL and > or =6.17 ng/mL) showed no increased risk of miscarriage (odds ratio, 0.84 and odds ratio, 0.74, respectively). Low folate levels were associated with a significantly increased risk of miscarriage when the fetal karyotype was abnormal (odds ratio, 1.95) but not when the fetal karyotype was normal (odds ratio, 1.11) or unknown (odds ratio, 1.45). More on low folate status…

Having both low folate and vitamin B6 increases the risk of miscarriage four‐fold

Homocysteine, folate, and vitamins B6 and B12 concentrations were measured in plasma obtained before conception. Mean vitamin B6 concentration was lower in patients than in controls (34.0 versus 37.9 nmol/L). In addition, the risk of miscarriage tended to increase with decreasing plasma vitamin B6 and folate concentration, although the significance of these trends was further reduced in logistic models that included age, body mass index, and both vitamins. The risk of miscarriage was four‐fold, higher among women with suboptimal plasma concentrations of both folate and vitamin B6 (folate less than or equal to 8.4 nmol/L and vitamin B6 less than or equal to 49 nmol/L) than in those with higher plasma concentrations of both vitamins (odds ratio 4.1). Homocysteine and vitamin B12 status were not associated with miscarriage risk.

various vitamin pills

Biotin: Biotin deficiency is associated with insulin resistance, which is common in recurrent miscarriage. More on biotin…

Calcium: High blood levels are associated with increased risk of miscarriage. More on calcium…

Choline: Low choline levels reduce embryonic growth and cardiac development. Choline has also been shown to prevent birth defects. More on choline…

Chromium: May improve insulin sensitivity in women with PCOS, although chromium picolinate has been shown to cause birth defects at high levels. More on chromium…

Folic acid: Low folate is associated with a 47% increased risk of miscarriage; having both low folate and low vitamin B6 increase miscarriage risk by 310%. Folic acid may also reduce the risk for Down Syndrome. More on folic acid…

Magnesium: Low magnesium is associated with increased risk of miscarriage; one study showed 100% of infertile women who normalized their magnesium and selenium levels went on to produce children. Low magnesium may also be associated with birth defects. More on magnesium…

Multivitamins: lowered the risk of miscarriage by 57% in one study. More on multivitamins…

Phosphorus: low in women who miscarry. More on phosphorus…

Selenium: lower in women with repeat miscarriage. Also, 100% of previously infertile women went on to conceive within eight months of normalizing their selenium and magnesium levels. More on selenium…

Beta carotene: lower in women with recurrent miscarriage. More on beta carotene…

Vitamin B12: lower in women with recurrent miscarriage. More on vitamin B12…

Vitamin B6: lower in women who miscarry. Also, vitamin B6 may counteract the negative impact of stress hormones on fetal growth. More on vitamin B6…

Vitamin C: low in women who habitually miscarry. Also, vitamin C has been shown to increase progesterone levels. More on vitamin C…

Vitamin D: critical for fetal development; also lowers miscarriage risk by reducing inflammation. 93% of infertile women were found deficient in vitamin D. More on vitamin D…

Vitamin E: lower in women with recurrent miscarriage. However, high levels are also linked to miscarriage and premature rupture of the membranes. More on vitamin E…

Vitamin K: low levels of vitamin K lead to miscarriage and birth defects. More on vitamin K…



Here is a summary of foods that have been shown to affect one's odds of having a miscarriage:

milk in glass bottles

Dairy: causes miscarriage risk to drop by 33%, and improves fertility. Lowers homocysteine and insulin resistance. More on dairy…


Milk: causes miscarriage risk to drop by 40%. Also affects hormones. More on milk…


Cheese: causes miscarriage risk to drop by 50%. More on cheese…


Butter: causes miscarriage risk to increase by 100%. More on butter…


a bowl of brown eggs

Oil: increases miscarriage risk by 60%. More on oil…


Eggs: causes miscarriage risk to drop by 30%. More on eggs…


assorted fruits

Fruit: causes miscarriage risk to drop by 46% to 70% in various studies. More on fruit…


Fiber: lowers miscarriage risk in sheep, and improves fertility in humans. Also affects hormones. More on fiber…


Fish and Poultry: cause miscarriage risk to drop by 15% to 30% in different studies. More on fish and poultry…


a variety of vegetables

Vegetables: causes miscarriage risk to drop by 40% to 50% in two studies. More on vegetables…


Chocolate: causes miscarriage risk to drop by 19%. More on chocolate…


back to top
8 Things Your Doctor Wants You to Know About Your Miscarriage

February 4, 2018 · by ObDoctorMom


Miscarriage is one of the hardest (and most common) challenges women face. If you have not had a miscarriage yourself, you most certainly have a best friend, sister, or daughter who has. There are many myths floating around the internet, however there are a few important truths everyone should know about miscarriage.


couple sitting in sunset

  1. You aren’t alone. Miscarriage is common and occurs more frequently than you might think. Often, a miscarriage occurs before a woman even knows she is pregnant. If you include these cases in statistics, up to 50% all pregnancies end in miscarriage. However, the number is closer to 15-20% for recognized pregnancies.

  2. Most miscarriages occur in the first trimester, but they can also happen later too. Luckily this is rare after 13 weeks. It is often more traumatic emotionally and physically in later trimesters. Women who experience late second trimester or 3rd trimester fetal losses (the term used when occurs later in pregnancy) will have physiologic responses from their bodies that think they just had a child. Their breasts may engorge with milk, a painful reminder of what was lost.

  3. It’s not your fault.

  4. It’s not your fault. Bears repeating. Also, its okay to grieve an early pregnancy loss. You likely had hopes, expectations, and dreams already wrapped up around this pregnancy. It may take a while to recover.

  5. man consoling woman
  6. Up to 80% of pregnancy tissue from first trimester miscarriage is chromosomally abnormal- meaning that there was a genetic problem with the developing baby.

  7. There has been debate over the amount of time you should wait after a miscarriage before trying again, but newer research shows that in most cases you can start trying again with the next cycle. Although, 3 months is a commonly quoted and may give you more time to heal physically and emotionally.

  8. The fact that you got pregnant is a good sign that you will be able to get pregnant again.

  9. You have 3 options when a miscarriage occurs- make sure you discuss all 3 with your doctor to determine the best course of option for you.

Expectant: this means waiting for your body to complete the miscarriage on its own. It may include moments of severe cramping and bleeding. The timing can be unpredictable, but you may be able to avoid a procedure if this is important to you. However, if the bleeding is severe you may still need medical intervention.

Medication: If you haven’t started bleeding yet, a pill can help your body to start the process once miscarriage is confirmed. This gives you a measure of control over when the process will start. It is successful in most cases, but sometimes you may still ultimately need a procedure if everything does not pass on its own.

Surgical: The procedure is called Dilation and Curettage “D & C”. This is a minor procedure to remove the contents of the uterus (failed pregnancy). Some women prefer this option as bleeding and cramping time is limited after the procedure. The process is over sooner and may cause less interruption for women who may need to be back at work, or have other children at home dependent on their care. There are risks with any surgical procedure, and although minor, must also be considered.


crib with stuffed toy but without baby

Since many people wait to tell family and friends about a new pregnancy until safely out of the first trimester, it can be a lonely experience if you go through a miscarriage without the support of your loved ones. In recent years, women have become more vocal about miscarriage and this has helped women feel less alone when it occurs. Don’t be afraid to reach out to others during this time. Be sure to discuss any concerns with your doctor and don’t lose hope about what the future may bring.

original article on ObDoctorMom.com


back to top
7 Things I Wish I Knew Before Freezing My Eggs

February 12, 2018 · by Christine Huang


Last February, I Decided To Freeze My Eggs.

I was 34, single-ish (I had been dating someone across the country for several months off and on, but it wasn't proving out to be anything serious), and my employer had recently added elective oocyte cryopreservation (the technical term for egg freezing) as a new benefit.

At the time, I saw it as pretty much a no-brainer for anyone thinking about getting pregnant later on and wondering if they'll have fertility problems: toss my restless eggs in a freezer and worry about all that baby stuff later? For free*?! (*Soon I would discover that, even with the procedure largely covered by my company, it was very much *not* free. But more on that later...)

A handful of my friends had gone through the process already. Most of them, like me, were unmarried, in their 30s, and not planning on baby making anytime soon. They all assured me that the whole thing wasn't nearly as bad as it sounded; that it was becoming more and more common and that if my employer was paying for it. I really had nothing to lose.

So I did it. Sometimes I have a hard time remembering it even happened, it was such a blur. But looking back on the entire experience a year later, I'm struck by how much I didn't know going into the whole ordeal that may have changed my decision to do it. I wish I had researched it a bit better and taken the time to mull it over before jumping into the growing, but still quite small pool of fertility preservationists.

So I'd like to pass these small bits of wisdom to you.


intropective woman sitting on windowsill looking out

Note: This is my personal experience with the egg retrieval process, and not everyone who undergoes egg freezing will have the same thoughts, feelings, and experiences that I did.

If You're Considering Egg Freezing, Here Are The 7 Things I Wish I Had Known – And That You Should Consider – Before Taking The Plunge.

  1. Your Frozen Eggs May Result In A Real-Life Baby. But Don't Count On It.

    Science is pretty f*ing amazing. The fact that egg freezing exists — that there is even the slightest chance that a tiny frozen oocyte floating around in a freezer somewhere in Midtown Manhattan might result in a healthy, human being 10 years down the line — is astounding.

    That being said: the science behind all of it is still relatively new. The first reported pregnancy resulting from frozen oocytes was in 1986 — and only about 5,000 births from frozen eggs have been reported since. As such, reliable data around success rates is largely limited, confusing, and inconclusive at best.

    technician working in laboratory

    According to the American Society for Reproductive Medicine (ASRM), the chance that any given frozen egg will result in a baby (even when the mother is younger than 38) ranges from 2-12%. During the egg-collection process, hormone stimulation treatment is used to help patients produce more eggs than they would during a normal cycle, so that multiple eggs can be collected and frozen.

    But even with a bounty of a baker’s dozen eggs or more (which would be considered a very successful round of egg collection and freezing) — the chances that the eggs will survive freezing, thawing, fertilization, and then result in a successful implantation and pregnancy are often very low. This is especially true for women who freeze their eggs after age 35; who are trying to get pregnant in their 40s; and who underwent treatment using an older, slow-freezing technique.

    While fertility clinics note that recent studies show a 90+% survival rate of frozen eggs using a newer vitrification technique — that figure only accounts for the freezing and thawing part of the process. It says nothing about the likelihood of fertilization and a successful to-term pregnancy. (And as this heartbreaking story demonstrates — it is disappointment in those final stages that can be the most traumatic and agonizing.)

    So — long story short: freezing your eggs is faaaaar from an insurance policy. The reality is, while you are giving yourself another (small) chance at having a child later in life — you shouldn’t count on it as a solid Plan B. It’s a Plan C at best — and a pretty stressful one at that.


  2. There will be blood. And needles. And DIY home chemistry involving strange solvents and powders and stuff that can all be very frightening. Prepare yourself.

    Buzzfeed's Christine Huang's chemistry test kit for egg freezing

    If you’ve done any preliminary research, you know that the scariest part of this whole thing won’t be the egg retrieval procedure itself (though, to be fair, the idea of a needle traversing through your vagina and into your ovaries to slurp out a bunch of hormonally induced eggs will take a minute to get comfortable with.)

    No — it’s the two weeks leading up to the procedure that the real fun happens. And by “fun” I mean a rigorous schedule of twice-daily, self-administered hormone injections that would make even the most practiced factory chicken tremble.

    So I’m not going to sugarcoat this.

    Waking up at the buttcrack of dawn every other day to get your blood drawn at a cold, depressing fertility clinic; shooting yourself with a syringe full of hormones twice every day (the moment you wake up and every night before you go to bed); feeling — and watching — as your ovaries swell to several times their normal size within the course of days — none of it is easy. It gets better after a couple of times, but those first few days will be scary (and for those with any discomfort around needles — straight up harrowing). And on top of all that — some of the medicine requires precise mixing of powders and solvents, temperature control, and timing. And if you mess up any one of those variables, it can be a big deal and ruin your whole retrieval cycle.

    That being said: while by no means a piece of cake — it’s all doable. After the first couple of days, the shots become routine and the mixing and timing almost second-nature. You learn what tips and tricks work for you. For me, it was icing the area for your shots 10-15 minutes before each one, injecting the solution very slowly so as to make its entry into your system less shocking (and therefore less painful), and recording each shot location and timestamp in my notepad app to ensure I wasn’t missing doses and wasn’t shooting myself repeatedly in the same place. Truth be told: the shots themselves don’t really hurt that much. The needles are so thin and small they’re hardly painful. But wrapping your mind around all of it, and convincing yourself this is worth doing for 14 or so days, can be tough. That’s why it’s important to remind yourself that yes, this will suck —but it’s all tolerable with the right attitude, organization and discipline. I’m a total disorganized wimp, and I survived. So let that be an inspiration to you all!


  3. Health risks and complications are uncommon — but they do happen. And some of them can be life-threatening.

    surgeon in dark room over operating table

    I didn’t know that you could die from egg freezing. (It’s super rare and probably won’t happen to you — but it can happen.) I also didn’t know that the long-term effects of extended and recurring hormone stimulation are still unclear. So before you decide to go through with the process, read up as much as you can about all the risk factors involved (ovarian torsions, ovarian hyperstimulation syndrome, hormonal side effects and retrieval complications, and the emotional risks of this procedure...to name a few.) Here’s a good place to start reading about the side effects of freezing your eggs. While the worst case scenarios are definitely in the minority — I would still advise being as informed as possible about any possible risks before committing yourself to this elective procedure.


  4. Egg freezing is a lonely, emotionally taxing process. There will be moments of “Is this my life, now?” reckoning. Don’t be afraid to lean on friends, family, and community to help you through it.

    One moment I was lying supine on a hospital gurney, legs in stirrups, listening to Kansas blaring from a shitty radio while a group of doctors and nurses nonchalantly scuffled around me prepping various drugs and apparati for my egg retrieval. The next, I was staring out the window onto a big parking lot, unsure of where I was or what had just happened. My friend/ersatz partner Brent appeared by my bedside, and I started putting together the pieces of where I was (the hospital) and what I had just done (scooped out my 20 factory-farmed eggs). The anesthesia had rendered me pretty useless, so Brent escorted me home in a taxi while I slowly regained mobility and full consciousness. We ordered food and he hung out with me until I fell asleep. Without him, I don’t know how I would have managed to get through that day.

    You’re freezing your eggs because for whatever reason, you are not in a place in your life to start a family, yet there is a piece of you that knows you still want the chance one day. That can be a lonely reality to come to terms with.

    woman seated on stone steps

    But don’t let that make you turn inward or alienate yourself from people who want to support you through what will be an emotionally stressful process. I was lucky to have great friends and family with whom I was very open about my fears and experience. I also had two friends who had gone through multiple egg retrieval cycles before and who offered their help or guidance any time of day, with any issue. My on-again, off-again boyfriend in California at the time was also a rock during the process — even FaceTiming with me the first couple of times I took my shots. I knew they were in my corner — even if only virtually — which helped me face each day without breaking down.

    And you’ll also be pleasantly surprised by the number of welcoming, helpful communities there are online to support you — and even make you laugh. BuzzFeed’s own Doree Shafrir has built a thriving community around her fantastic podcast Matt and Doree’s Eggcelent Adventure, which chronicles (with refreshing candidness and levity) her experiences in IVF with her partner, Matt. Though focused primarily on people undergoing IVF rather than egg freezing, Matt and Doree’s podcast and facebook group helped me feel like I wasn’t alone, and that there was a lot I could learn about myself and even laugh about through this process. I highly recommend you find and join support groups like these to learn more and prepare for your procedure.


  5. If you don’t want to be pregnant now, but there’s a sperm you’re not mad at — consider freezing embryos (fertilized eggs) instead of eggs.

    couple looking towards horizon

    If you’re with a partner with whom having a family with is not completely out of the question — or if you’re considering a sperm donor for future baby potential, freezing an embryo might be something worth considering. After reading through many forums and blogs on the matter, I found that one of the biggest regrets among women struggling through unsuccessful IVF rounds (using both fresh and frozen eggs/embryos) is that they didn’t freeze embryos at an earlier age. Eggs are more fragile than embryos, meaning there is a higher chance that some can be lost in the freezing, thawing, and fertilization process. So if a decent sperm donor is in the picture now — it won’t hurt to look into options beyond egg preservation.


  6. During the hormone treatment, it’s normal for your emotions to be all over the place. Don’t let it scare you. But don’t do anything you’ll regret.

    One of the best pieces of wisdom I received from a friend who had gone through this process was, “Do NOT make any big decisions during your hormone treatment. Your brain isn’t your brain for those weeks. Don’t trust it.” I tried to heed her advice. But when hormone injections push your estrogen to 10x times their baseline level, and your stomach has bloated to the size of a small watermelon, and you’re alone, staring at yourself in the mirror for the 13th day in the row jabbing a needle into your thigh — feelings get stirred. It’s okay to feel not okay. It’s important to step back and remind yourself that what you’re doing is a big deal on a cosmic level: you’re using science to control your future reproduction. It’s terrifying, miraculous, empowering, and traumatizing at the same time. You’re going to have mood swings at times. The key is to be ready for them, and to set up preventative measures to keep yourself from spiraling into a hormonally-charged tailspin. Have a sponsor to text whenever you’re feeling especially emotional. Delete your ex-partners’ phone numbers. Give your social media passwords to a good friend for the month. Do all that you can to protect yourself from letting the hormones get the best of you.


  7. young isolated woman sitting in corner

  8. Finally: this sh*t is EXPENSIVE

    Even if elective oocyte cryopreservation is technically covered by your employer — prepare to shell out at least $1000 for this whole thing — and without coverage, in the ballpark of $10k. And some costs you should consider (that likely will *not* be covered by insurance, no matter how plush your company benefits) are…

    • $500-1500/year storage fee to pay to keep your lil’ buggers on ice
    • $600+ for fertility drugs (much of which you won’t actually use, but you’ll be instructed to purchase more than enough of, “just in case”)
    • $1K-10K for another round of egg retrieval, if the first round results in fewer eggs than you’d anticipated (they say a “good round” is 10 eggs or more, but it could be less or more)

    TL;DR: With insurance/employer coverage or not: financially, this is no small investment. Fertility treatments are glimpses into the wild bio-hacked future. Expect to pay for the privilege of participating in this little experiment.

  9. original article on BuzzFeed by Christine Huang


laboratory technician at work

back to top
Definitions
  • RPL Definition: Two to three consecutive spontaneous abortions (miscarriages) before 20 weeks gestation.
  • Sporadic Abortion: A single pregnancy loss is a common event occurring in 10-20% of all human pregnancies.
Incidence
  • How Many Women Are Affected: Approximately 1-5% pregnant women have a diagnosis of RPL (40,000 - 200,000 U.S. couples/year).
  • What Might Happen After Miscarriage: 49% of women with two consecutive losses and no live-born children will have a loss in their next pregnancy, whereas 29% of women with two losses and at least one live-born child will have a loss in their next pregnancy.
  • Is Age a Factor in RPL: The incidence of a single miscarriage increases with female age in both normal and in RPL patients. The basic normal miscarriage rate is 10% per pregnancy ages 15-29 and as high as 55% for women >44 years old. This normal age dependent increasing miscarriage rate compounds the problem for women with RPL.

POTENTIAL CAUSES of RPL & DIAGNOSTIC TESTS

At REIG, we have years of experience helping patients with recurrent pregnancy loss have healthy pregnancies. We excel at diagnosing, counseling, and treating simple and complex RPL conditions. We are willing to consider less commonly accepted causes of RPL, such as allo-immune causes (where the normal mechanisms that prevent a woman from rejecting her fetus don’t work). The field of Reproductive Immunology is expanding, and has brought hope to many women.


RPL Causes, Diagnostic Tests, Potential Treatments
Cause Diagnosis Potential Treatment
Chromosomal (familial genetics) Karyotype both parents IVF with PGD to pick normal embryos
Chromosomal due to age Ovarian reserve testing CoQ10, DHEAS, acupuncture, IVF with PGD, egg donation
Uterine HSG, saline sonogram, MRI Remove fibroids, scar tissue, cut septum
Endocrine Prolactin, thyroid, Adrenal Correct thyroid or pituitary dysfunction with medication; meditation, acupuncture
Polycystic Ovarian Syndrome Hemoglobin A1C, 2 hour Insulin tolerance test, ultrasound Weight loss, nutritional changes, exercise, supplements
Infectious Endometrial biopsy for TB culture if suspicious (patient from areas with endemic TB). Hysteroscopy may be necessary for diagnosis Antibiotics, surgery to cut scar tissue from infection
Toxins Smoking, chemical exposure at work, Phthalates (BPA) in plastics, xenoestrogens in foods Smoking cessation, avoid phthalates (BPA), polishes, hardeners, glues, and solvents
Inflammation Assumed with obesity, rheumatoid diseases, PCOS Control PCOS, Vitamin D, fish oil, dietary calcium, selenium if hypothyroid
Dietary/Nutritional Low folate levels, alcohol, smoking, low body weight Folate supplements, fruits and vegetables daily
Blood Clotting (Thrombophilia) Factor V Leiden, MTHFR, Antithrombin III, Protein S and C, Homocysteine Folate supplementation, (methyltetrafolate), Heparin and Aspirin
Auto-immune Anti-Phosphatidyl serine, LAC, Anti-cardiolipin antibody, Beta-2 glycoprotein, anti-thyroid antibody Thyroid hormone, Heparin and Aspirin, IV Immunoglobulin, IV Intralipid
Allo-immune TH1:Th2 cytokine ratio, NK cells IV Immunoglobulin, IV Intralipid
Male Factor Semen analysis, Sperm chromatin structure analysis Antioxidants, especially Vitamin C, selenium, zinc

  1. PARENTAL GENETIC ABNORMALITIES

    The incidence of chromosomal abnormality in couples experiencing RPL is 3-5%. Diagnosis is made by chromosome testing (karyotype) of a patient’s blood sample. Most RPL patients with a chromosome abnormality have no physical evidence of a problem other than their history of RPL itself. Couples with a family history of genetic abnormality or miscarriage should be offered genetic counseling as well as genetic testing. (2)

    Types of chromosomal mistakes that cause RPL
    1. Translocation: genetic material is exchanged between chromosomes. If any genetic material is lost then the mutation is “unbalanced” and abnormal sperm or eggs may form. A carrier appears normal, since all their genetic material is present, just mixed partly on the wrong chromosomes. When pregnancy occurs, a parent only gives half of the chromosomes, so there is a high likelihood that the child may not get a complete set of chromosomes, leading to either miscarriage, or a baby born with severe birth defects.
    2. Chromosome inversion: chromosome breakage and re-attachment with a segment turning the wrong way. This causes misreading of the flipped portion. Again, when a parent passes half a set of chromosomes to the fetus, missing or misread portions of the chromosome lead to RPL or severe birth defects.
    3. Single gene mutations: These are common causes of genetic diseases, such as Cystic Fibrosis (CFTR gene), or Sickle Cell Anemia (Hemoglobin Beta gene found on chromosome 11). There are many genes involved in normal development of a baby, most of which are unknown. The Human Genome Project will likely provide explanations for many illnesses and causes of RPL.

    Normal Male Karyotype (46 XY) from blood sample

    Figure 1 - Normal Male Karyotype (46 XY) from husband’s blood sample

    Normal Male Karyotype (46 XY) from blood sample

    Figure 2 - Male karyotype with abnormal exchange of genetic material between chromosomes 9:22 (Translocation)

    Treatment for chromosomal abnormalities
    1. Prenatal diagnosis with either amniocentesis (removing fluid from around the baby at 16-18 weeks of pregnancy) or Chorionic Villus Sampling (CVS, biopsy of the placenta, done at 10-11 weeks). Termination of pregnancy is possible. Testing allows preparation for potential medical problems at birth.
    2. There is now a blood test that can find fetal cells in the mother’s blood stream. Because it doesn’t invade the fetal space, it is called non-invasive prenatal testing (NIPT), and can be done at 8-10 weeks of pregnancy. It doesn’t test for every chromosome at this time, but advances occur frequently in this field.
    3. In Vitro Fertilization with preimplantation diagnosis can allow a couple with a known chromosomal problem to have a healthy baby by testing the embryos and picking one with normal chromosomes for transfer. (2)

  2. UTERINE ANATOMIC ABNORMALITIES

    It is estimated that 10-20% of RPL results from anatomic abnormalities of the uterine cavity. Abnormalities are diagnosed with an X-ray procedure (hysterosalpingogram - HSG) or an ultrasound procedure (sonohysterogram – SHG) or Hysteroscopy (looking inside the uterus).


    Examples include:
    Congenital abnormalities

    One uterine abnormality is a septate uterus. If implantation occurs on or near the septum, then blood flow is poor and there is a higher risk of miscarriage. A septum can be excised with hysteroscopy and yields excellent results, although there is a risk of scar tissue forming.


    HSG film of septate uterus

    Figure 3 - HSG film of septate uterus

    Blausen medical illustration of hysteroscopic uterine evaluation

    Figure 4 - Hysteroscopic Uterine Evaluation

    uterine septum prior to resection

    Figure 5 - Uterine Septum Prior to Resection

    Fibroids

    Fibroids are benign growths that are very common and often are asymptomatic. If fibroids grow inside or close to the uterine cavity, there is a higher risk of abnormal bleeding and miscarriage. If there are multiple fibroids in the uterine wall, then blood flow to the uterine cavity may be affected, and this can lead to increased risk of miscarriage. Removal is usually successful, although scar tissue can form, depending on position and size of tumors.


    illustration of fibroids

    Figure 6 - Fibroids

    Asherman’s Syndrome

    Asherman’s Syndrome involves scar tissue inside the uterus. This can be caused by bacterial infection, surgery on the uterus for miscarriage or pregnancy termination (D&C), prior surgery to remove polyps or fibroids, or Tuberculosis. Treatment involves Hysteroscopy to look inside and remove scar tissue from the uterine cavity. This surgery is usually corrective, but rarely a gestational carrier may be required.


  3. HORMONAL & METABOLIC PROBLEMS:

    The incidence of endocrine abnormalities in women with RPL is approximately 10-15% and may be much higher if patients with PCOS are included. Endocrine factors may include hyperprolactinemia (pituitary prolactin overproduction), thyroid dysfunction, and Diabetes. Correction of these problems are critical prior to attempting conception to reduce fetal harm, improve fertility and reduce risk of miscarriage.

    Low dietary folate is associated with an increased risk of miscarriage. Eating fresh fruit and vegetables daily or most days was associated with a halving in the odds of miscarriage. (3)

    Consumption of dairy products (milk, yoghurt, cheese) and chocolate was also associated with decreased odds of miscarriage.

  4. ADVANCED REPRODUCTIVE AGE

    Defined as female age of 35 and above. Many women assume that reproductive success will naturally follow a healthy lifestyle. Unfortunately, living a healthy life does not change the fact that a woman is born with all of her eggs. A good number of women with unexplained infertility or RPL are experiencing accelerated reproductive aging. Aging eggs are more likely to be genetically abnormal. Thus, advancing female age (and increasing male age) will cause an increased number of genetically abnormal embryos.

    Diagnosis is based on estradiol and FSH (follicle stimulating hormone) plus antral follicle count that are checked early in the menstrual cycle. AMH (anti-mullerian hormone), which reflects the number of healthy eggs growing for that menstrual cycle can be tested throughout the cycle. These tests can help identify even young women with diminished ovarian reserve who need aggressive fertility therapy, as well as identifying a reason for miscarriage. Ovulation induction with fertility drugs may increase the number of eggs that ovulate each month, thereby increasing the chance of a normal egg developing.

  5. POLYCYSTIC OVARIAN SYNDROME (PCOS)

    This disorder of androgen excess, anovulation, and altered insulin metabolism, “insulin resistance” is associated with up to a 50% miscarriage rate in patients older than 35 years. Older patients may have a higher rate when the effects of PCOS and age are combined. Typical diagnostic tests include testosterone and DHEAS levels, 2 hour insulin/glucose tolerance test, FSH and LH levels, and ovarian ultrasound evaluation. Abnormalities, such as thyroid disease or hyperprolactinemia, should also be excluded. Patients with significant insulin resistance and high testosterone levels may be at greatest risk of miscarriage, as are obese patients.

    Treatment consists primarily in treating insulin resistance with dietary and lifestyle changes to reduce weight. Folate absorption is reduced in obese patients along with other metabolic problems that increase risks of fetal harm and complicated pregnancy. Metformin has been shown to reduce the risk of miscarriage, and is prescribed throughout the first trimester of pregnancy. Nutritional supplements (chromium, cinnamon, ginseng, alpha-lipoic acid), dietary changes (low glycemic diet) and behavior modification (increased exercise and mind-body medicine for stress relief such as biofeedback, yoga, meditation, music therapy) with allow many women to overcome PCOS and conceive a child naturally, while reducing the risk of miscarriage.

  6. IMMUNOLOGIC CAUSES of MISCARRIAGE

    Autoimmune: antibodies are directed against one’s own organs. This includes illnesses such as Systemic Lupus Erythematosus, Rheumatoid Arthritis, and thyroid dysfunction. The antiphospholipid antibody syndrome (APS) is defined by recurrent pregnancy loss and thrombosis (blood clots) in the presence of antiphospholipid (aPL) antibodies. Phospholipids are an integral part of cell wall development and help blood vessels form in the placenta. aPL antibodies attach to the phospholipids and affect blood vessel development. Treatment consists of blood thinners, Heparin and aspirin.

    Alloimmune: A normal pregnancy consists of the growth of fetal tissue that has foreign antigens from the father. The mother’s immune system generally produces blocking antibodies to keep her immune system from attacking the foreign cells of the fetus. Immune cells secrete messengers called Cytokines that can either turn on attacking cells, or turn on anti- inflammatory cells. These cells may cause maternal harm (allergies), but in general they help to protect the pregnancy.There are two main types of immune cells involved in maternal tolerance of pregnancy: attacking cells are called T-helper cells 1 (TH-1) and anti-inflammatory cells are called T-helper cells 2 (TH-2). The ratio of these cells appears to represent the activity of the maternal immune response to pregnancy (TH-1:TH-2). Studies have shown that women with recurrent miscarriage exhibit primarily TH-1 cytokines, whereas healthy women exhibit decreased TH-1 cytokines and increased TH-2 cytokines. (6) Treatment is controversial, and consists of immunosuppression.

  7. LUTEAL PHASE DEFECT (LPD) and Endometrial Defects

    LPD is a controversial cause of RPL. This can be a disorder of either low progesterone production by the ovary or low uterine response to progesterone. Endometrial biopsy and serum progesterone testing have been shown to provide highly inconsistent results in numerous studies. Treatment primarily consists of inducing ovulation to produce improved egg production, which, in turn, may correct a luteal phase defect. Patients have been administered progesterone supplementation in addition to ovulation induction in an effort to improve success rates. A recent study of progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (7)

    Endometrial Defects

    Suboptimal progesterone production and uterine pathology may result in endometrial defects. In some cases, endometrial defect may occur despite normal progesterone levels and in the absence of obvious uterine pathology, in which case it is unexplained. Newer genetic markers of estrogen and progesterone effect in the uterus may provide more accurate diagnostic testing. Cell adhesion markers have been identified, and shown to be involved in attachment of the blastocyst to the endometrium. (8) Endometrial Function Testing (EFT) is a specialized biopsy that can show whether the endometrium is normally producing the “sticky glue” necessary for normal implantation and embryo and placental development. (9)

  8. TOXIN EXPOSURE
    woman smoking cigarette

    Toxins such as ionizing radiation, mercury, lead and alcohol are confirmed teratogens, and could contribute to pregnancy loss. Hyperthermia (fever or high body temperature during early pregnancy) is a suspected teratogen. Cigarette smoking has been linked to miscarriage, ovarian damage, and diminished ovarian reserve and earlier than expected menopause. The teratogenic effect of pesticides and herbicides is unknown, but of concern. It is unknown whether exposure to food additives, such as artificial sweeteners, contribute to recurrent pregnancy loss. It is advisable to eliminate toxins at least three months prior to conception.

    Recent reports of reproductive damage from phthalates (BPA, etc) are suspicious for increased miscarriage risk and should be avoided as much as possible. A study of women working in salons with high exposure to hair dye, solvents and nail polish showed an increased risk of gestational diabetes, and evidence of SGA infants (small for gestational age), as well as premature ruptured membranes and placenta previa. (5)

  9. RECURRING EMBRYONIC ANEUPLOIDY

    Approximately 50% of couples experiencing RPL have no cause identified after routine testing. Many of these patients may be experiencing recurring embryonic genetic abnormalities incompatible with survival (aneuploidy). The risk of chromosome abnormalities (aneuploidy) in embryos increases primarily with female age, and to a lower extent, with increasing male age. However, with the increasing use of IVF/PGD, studies have shown very high rates of embryonic aneuploidy in previously unexplained RPL patients starting as young as their mid to late 20’s. Thus, recurring embryonic aneuploidy appears to be a common cause of RPL in patients where no other cause has been identified regardless of age. (2)

  10. THROMBOPHILIC DISORDERS (Excessive blood clotting)

    Hypercoagulable conditions that are either inherited or acquired may cause RPL and pregnancy complications. Testing is generally performed if there is a significant family or personal history of thrombosis or early cerebrovascular events (stroke). Prior unexplained fetal death (loss of heartbeat after 8 weeks), severe fetal growth restriction with no other identifiable cause, and early toxemia (preeclampsia) during pregnancy are indications for testing. Diagnosis is based on blood testing for Factor V Leiden mutation, Prothrombin gene mutation, Protein C and S deficiency, and hyper-homocysteinemia (MTHFR mutation). Treatment generally consists of heparin and aspirin. If elevated homocysteine or MTHFR mutation is present, then supplementation with folate and vitamins B6 and B12 is indicated.

  11. MALE REPRODUCTIVE ABNORMALITIES

    Males with significant, persistent abnormal sperm morphology (abnormal shape) may father a higher number of genetically abnormal embryos. Diagnosis requires several semen analyses. Sperm testing with DNA fragmentation analysis may also predict the presence of a higher than average percentage of genetically abnormal sperm. It is possible that some cases of RPL may be related to increasing male age – particularly in men over 40 years old.

    illustration of abnormal sperm morphology 1
    illustration of abnormal sperm morphology 2


    If varicocele (varicose veins of the scrotum) is present, surgical correction may improve DNA fragmentation and potentially reduce miscarriage rate. Antioxidant supplementation, especially Vitamin C, zinc, selenium, and CoQ10 may also improve sperm DNA function.

  12. INFECTIOUS CAUSES of RPL

    Maternal infections, such as rubella, cytomegalovirus, toxoplasmosis or herpes can have devastating effects on a fetus, causing severe birth defects or miscarriage, but they do not cause recurrent pregnancy loss. Mycoplasma has been suspected of causing RPL, although recent studies have refuted this. Bacterial vaginosis (BV), is a complex alteration in vaginal flora involving multiple bacteria, including Mycoplasma and Gardnerella vaginalis. These changes are accompanied by a depletion in vaginal lactobacilli. Infection with BV has been associated with increased risk of first trimester miscarriage in patients undergoing IVF. Probiotics are being studied as a method to maintain female vaginal and bladder health and as a treatment option for recurrent bacterial vaginosis, urinary tract infection, yeast vaginitis, and sexually transmitted infections. Probiotics have been widely used by patients to treat bladder and vaginal infections, but research has not yet shown a benefit in reducing miscarriage risk. (12)

    Tuberculosis can cause pelvic infection, leading to infertility and miscarriage. Patients can be otherwise asymptomatic. Diagnosis requires endometrial biopsy to obtain tissue, and the organism may take over a month to grow in culture. Treatment with anti-tuberculosis drugs will often be curative, but scarring may occur, requiring surgery to correct. Scarring is sometimes severe enough that pregnancy is not possible, and a gestational surrogate may be necessary.

  13. STRESS
    relaxed cat just hanging in the limb of a leafy tree

    A British study (1) showed that being happy, relaxed or in control was associated with a 60% reduction in odds of miscarriage. Conversely, women who reported feeling ‘stressed’, ‘anxious’, ‘depressed’, ‘out of control’ or ‘overwhelmed’ in the first 12 weeks of pregnancy had much higher odds of miscarriage than those who described themselves as happy, relaxed or in control. Women who reported feeling ‘other’ emotions (which tended to be negative, including guilt and fear) also had increased odds of miscarriage.

    There was a strong trend in increasing odds of miscarriage with increasing number of stressful or traumatic events. The most common event was having a stressful or demanding job. (1)

  14. PSYCHOLOGICAL ASPECTS and SUPPORT MEASURES

    The tragedy of miscarriage has traditionally been private, an event grieved largely by the mother, on her own. Health-care professionals often advise these women that the sadness would grow less pronounced over time, especially following a successful pregnancy.

    One study found that patients' experiences of pregnancy loss were embedded within their experiences of infertility and medical treatment, and shaped by their significant investment in having a child. A significant feature was their marked ambivalence regarding future reproductive options after their pregnancy loss, reflecting a unique overlay of prominent anxiety in their grief experience. (13)

REFERENCES
  1. Maconochie N, Doyle P, Prior S, Simmons R. Risk factors for first trimester miscarriage—results from a UK-population-based case–control study. BJOG 2007;114:170–186.

  2. George L1, Granath F, Johansson AL, Olander B, Cnattingius S. Paediatr Perinat Epidemiol. 2006 Mar;20(2):119-26. Risks of repeated miscarriage.

  3. Lena George, MD; James L. Mills, MD, MS; Anna L. V. Johansson, MSc; Anna Nordmark, MSc; Bodil Olander, MD; Fredrik Granath, PhD; Sven Cnattingius, MD, PhD JAMA. 2002;288(15):1867-1873. doi:10.1001/jama.288.15.1867. Plasma Folate Levels and Risk of Spontaneous Abortion.

  4. Elisabeth Clare Larsen, Ole Bjarne Christiansen, Astrid Marie Kolte, and Nick Macklon. BMC Med. 2013; 11: 154. New insights into mechanisms behind miscarriage.

  5. Quach T, Von Behren J, Goldberg D, Layefsky M, Reynolds P. Int Arch Occup Environ Health. 2014 Dec 14. Adverse birth outcomes and maternal complications in licensed cosmetologists and manicurists in California.

  6. T.C.Li, M.Makris, M.Tomsu, E.Tuckerman and S.Laird, Human Reproduction Update, Vol.8, No.5 pp. 463±481, 2002. Recurrent miscarriage: aetiology, management and prognosis.

  7. Arri Coomarasamy, M.B., Ch.B., M.D., Helen Williams, B.Sc, et al. N Engl J Med 2015; 373:2141-2148 November 26, 2015. A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.

  8. Tanya Timeva, Atanas Shterev, and Stanimir Kyurkchiev. J Reprod Infertil. 2014 Oct-Dec; 15(4): 173–183. Recurrent Implantation Failure: The Role of the Endometrium

  9. Kliman, H. J., et al. "Optimization of endometrial preparation results in a normal endometrial function test®(EFT®) and good reproductive outcome in donor ovum recipients." Journal of assisted reproduction and genetics 23.7-8 (2006): 299-303. EFT is a test of the endometrium to predict how likely it is that implantation will happen.

  10. Elisabeth Clare Larsen, Ole Bjarne Christiansen, Astrid Marie Kolte, and Nick Macklon. BMC Med. 2013; 11: 154. New insights into mechanisms behind miscarriage.

  11. Holly B Ford, MD* and Danny J Schust, MD, Rev Obstet Gynecol. 2009 Spring; 2(2): 76– 83. MedGenMed. 2004 Mar 29;6(1):49. Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy.

  12. Reid G1, Burton J, Devillard E., MedGenMed. 2004 Mar 29;6(1):49. The rationale for probiotics in female urogenital healthcare.

  13. Harris DL1, Daniluk JC, Hum Reprod. 2010 Mar;25(3):714-20. doi: 0.1093/humrep/dep445. Epub 2009 Dec 19. The experience of spontaneous pregnancy loss for infertile women who have conceived through assisted reproduction technology. In-depth interviews with women who have experienced miscarriage after fertility therapy. Common responses included marked ambivalence regarding future reproductive options after their pregnancy loss, reflecting prominent anxiety in their grief experience.

back to top
What is Polycystic Ovarian Syndrome?

Polycystic Ovarian Syndrome (PCOS) is the most common endocrine disorder in women, affecting an estimated 5-10% of all women of reproductive age. It usually starts at the time of puberty, with an increased incidence of menstrual abnormalities, acne, facial hair, weight gain and infertility. If not controlled, it can lead to increased risks of uterine cancer, cardiovascular disease and a 7 fold increase in type 2 diabetes. For women trying to conceive a child, PCOS is a serious, common cause of infertility - nearly half of all female factor infertility cases can be traced to PCOS. When pregnancy occurs, the rate of first trimester miscarriage is as high as 30-50%.

medical illustration of normal ovaries and polycystic ovaries
Insulin resistance is a common finding in women with PCOS. The excess insulin causes abnormally high levels of male hormone production from the ovary, leading to acne on the face, breasts, back and abdomen, oily skin, and sometimes male pattern hair loss. Insulin also decreases the amount of sex-hormone-binding globulin from the liver, which means there is excess free androgen (male hormone) in the circulation. This causes negative cosmetic effects, but also affects blood pressure, and increases cardiac risk factors, with a decrease in HDL (good cholesterol) and an increase in LDL, triglycerides and VLDL (unhealthy cholesterol).


illustration of young woman with PCOS
Treatment of PCOS

The goals of treatment include control of insulin resistance and abnormal glucose levels, treatment of elevated lipids, treatment of anovulation and symptoms of androgen excess (acne and oily skin), prevention of abnormal uterine bleeding and treatment of infertility.

Given the complex endocrine and metabolic nature of PCOS, the treatment plan should be integrative, and may include insulin-sensitizers (glucophage, (Metformin), ovulation stimulants (clomiphene, letrozole or injectable gonadotropins), nutritional supplements (chromium, cinnamon, ginseng, alpha-lipoic acid), dietary changes (low glycemic diet) and behavior modification (increased exercise and mind-body medicine for stress relief such as biofeedback, yoga, meditation, music therapy) with allow many women to overcome PCOS and conceive a child naturally, while reducing the risk of miscarriage. Acupuncture calms sympathetic tone and may stimulate ovulation. Combinations of anti-insulin medications have been studied and may improve weight loss and ovulation.

Recent studies have investigated the use of N-acetylcysteine (NAC) in women with polycystic ovary syndrome (PCOS). N-acetylcysteine has been shown to have anti-inflammatory properties and is converted to glutathione, the main anti-oxidant in the body. Eight studies with a total of 910 women with PCOS were randomized to NAC or other treatments/placebo. Women with NAC had higher odds of having a live birth, ovulating , and getting pregnant as compared to placebo. However, women with NAC were less likely to have a pregnancy or ovulation as compared to metformin. There was no significant difference in rates of miscarriage, menstrual irregularity, acne, hirsutism, and adverse events, or change in body mass index, testosterone, and insulin levels with NAC as compared to placebo. The authors concluded that NAC showed significant improvement in pregnancy and ovulation rate as compared to placebo but longer follow-up periods are needed to examine clinical outcomes such as live birth rate.

Inositol is a member of the B-vitamins and a component of the cell membrane. It is believed that inositol increases the action of insulin in women with PCOS, thereby improving ovulation, decreasing testosterone, and lowering blood pressure and triglycerides. In a recent study, 25 women received inositol for six months. Twenty-two out of the 25 (88%) patients had one spontaneous menstrual cycle during treatment, of whom 18 (72%) maintained normal ovulation. A total of 10 pregnancies (40% of patients) were obtained. Generally, inositol is well tolerated but can cause nausea, fatigue, headaches and dizziness. No interactions with herbs or supplements are known. There is concern, however, that high consumption of inositol might exacerbate bipolar disorder. Inositol is sold as myo-inositol (most common in the U.S.) or d-chiroinositol. Dosage is 200 to 2,000 mg daily. Ovasitol is sold online and in health food stores, but may not have both components. Theralogix makes a high quality supplement with the appropriate ratio of myo-inositol to d-chiroinositol, important for egg health.

What next? Women who undergo treatment for PCOS but are still unable to conceive naturally are good candidates for assisted reproductive technologies, including IUI and IVF, and often experience high pregnancy success rates. Fertility drugs cause an increased risk of multiple birth, and ovarian hyperstimulation where the ovaries produce excess egg sacs during therapy. This can lead to fluid draining into the abdomen, blood clotting, and may equire draining of fluid or hospitalization.

Blausen illustration of assisted reproductive technology

Assisted Reproductive Technology - Blausen.com staff

PCOS patients are challenged by physical and emotional distress. There is not one simple treatment strategy for all patients, as each patient has her own unique combination of symptoms and disease manifestation. A complete evaluation to rule out other organ system problems (adrenal, thyroid, uterine, tumors) is necessary before treatment to improve the likelihood of a successful response and reduce risks of complications. An integrative approach often improves results.

There is ample evidence that physical activity may help in the prevention and management of type 2 diabetes. It is important that patients with this chronic disease remain regularly active. Both aerobic and resistance training appears to help with glucose control and weight loss, and reduce the risk of future diabetes and heart disease.


References
  1. PCOS Nutrition. Nutritionist driven website with great information about diet, exercise, supplements, and nutritionist consultation.

  2. Exercise and Type 2 Diabetes. Sheri R. Colberg, PHD, FACSM, Ronald J. Sigal, MD, MPH, FRCP(C), Bo Fernhall, PHD, FACSM, Judith G. Regensteiner, PHD, Bryan J. Blissmer, PHD, Richard R. Rubin, PHD, Lisa Chasan-Taber, SCD, FACSM, Ann L. Albright, PHD, RD, and Barry Braun, PHD, FACSM

  3. N-Acetylcysteine for Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. Divyesh Thakker, Amit Raval, Isha Patel, and Rama Walia

  4. Myo-inositol in patients with polycystic ovary syndrome: A novel method for ovulation induction. Papaleo E, Unfer V, Baillargeon J P, et al.
Resources

back to top
Endometriosis, a cause of female infertility, is a condition in which endometrial tissue, the tissue that lines the inside of the uterus, grows outside the uterus and attaches to other organs in the abdominal cavity such as the ovaries and fallopian tubes. Endometriosis is a progressive disease that tends to get worse over time and can reoccur after treatment. Symptoms include painful menstrual periods, abnormal menstrual bleeding and pain during or after sexual intercourse.

medical illustration of endometriosis by Bruce Blausen from Wikimedia

Blausen.com staff

The endometrial tissue outside your uterus responds to your menstrual cycle hormones the same way the tissue inside your uterus responds - it swells and thickens, then sheds to mark the beginning of the next cycle. The blood that is shed from the endometrial tissue in your abdominal cavity has no place to go, resulting in pools of blood causing an inflammation that forms scar tissue. The scar tissue can block the fallopian tubes or interfere with ovulation. Another form of endometriosis is the formation of ovarian cysts called endometrioma that may also interfere with ovulation.

The cause of endometriosis is unknown although there are a few theories. One theory suggests that during menstruation, some of the menstrual tissue backs up through the fallopian tubes into the abdomen where it implants and grows. Another theory indicates that it is a genetic birth abnormality in which endometrial cells develop outside the uterus during fetal development. If there is immune system dysfunction, endometrial cells may grow where they would normally be removed by immune cells.

A laparoscopy, an outpatient surgical procedure, is necessary to confirm a diagnosis of endometriosis after a medical history review and pelvic exam. After the initial diagnosis, your physician will classify your condition as stage 1 (minimal), stage 2 (mild), stage 3 (moderate) or stage 4 (extensive) based on the amount of scarring and diseased tissue found. Based on the stage of endometriosis, your physician will determine the best treatment plan for you. Once the diagnosis is made, endometriosis tissue may be treated with laser therapy, excision, or thermal (heat) therapy during surgery. This initial diagnosis and treatment may be sufficient to relieve pain or allow pregnancy to occur. Depending on the degree of disease, medication may be necessary to further shrink the disease.

medical illustration of laparoscopy by Bruce Blausen from Wikimedia

Blausen.com staff

Integrative approaches may help to reduce symptoms of endometriosis. Acupuncture and Chinese medicine may improve symptoms. Various herbs said to be helpful in relieving endometriosis and symptomatic pain include: Blue Cohosh, Cranberry, Plantain, St. John’s Wort, Peppermint, Valerian, Dong Quai, False Unicorn, Evening Primrose Oil, Chasteberry/Vitex, Black Cohosh, Uva Ursi, Couchgrass, Red Raspberry, Yam, and White Willow. Reduction in estrogen effect through detoxification of the liver is thought to lead to improvement.

Treatment of endometriosis may allow spontaneous conception to occur, but fertility treatment is often beneficial. Treatment may be as simple as stimulation of ovulation. Even for women with normal ovulatory menstrual cycles, there may be subtle ovulatory dysfunction, and even abnormality in the physical release of the egg at the time of ovulation. By stimulating more than one egg to mature, there is a higher likelihood of physical release of the egg, as well as an increase in follicular fluid that is released with the egg. This fluid may improve chances that sperm will reach the egg by diluting toxic factors secreted by endometriosis cells present in the pelvis.

If ovulation induction is unsuccessful, then adding intrauterine insemination may improve success rates by flooding the reproductive tract with sperm. In Vitro Fertilization ensures that sperm reaches egg, and that fertilization occurs. Embryo culturing and transfer directly to the uterus bypasses the fallopian tubes and reduces exposure of gametes to potentially toxic factors.

Resource

back to top

Adenomyosis, (ad-uh-no-my-O-sis) occurs when endometrial tissue, which normally lines the uterus, exists within and grows into the muscular wall of the uterus. The displaced endometrial tissue continues to act as it normally would — thickening, breaking down and bleeding — during each menstrual cycle. Blood will gradually collect in the muscle, and an enlarged uterus and painful, heavy periods can result.

Symptoms most often start late in the childbearing years after having children, but can be a cause of infertility. If adenomyosis is severe, it can interfere with normal blood flow to the lining of the uterus, and prevent normal implantation and pregnancy from occurring.

The cause of adenomyosis remains unknown, but the disease typically disappears after menopause. For women who experience severe discomfort from adenomyosis, certain treatments can help, but hysterectomy is often recommended. Sometimes, adenomyosis is silent — causing no signs or symptoms — or only mildly uncomfortable. For women who want to maintain their fertility, medications can shrink the adenomyosis, and allow normal implantation and pregnancy to occur. More info on adenomyosis…



medical illustration of Adenomyosis

back to top

Women today spend half their lives in menopause. Menopause is a natural transition but the loss of ovarian function can lead to abrupt changes. In particular, menopausal women note cognitive dysfunction often describing difficulties with memory and focus. Menopausal symptoms like hot flashes and night sweats may dramatically impact sleep. Women may experience bone loss, vaginal dryness, and a higher risk of cardiovascular disease.

What Happens with Menopause

Women going through menopause may feel that they have accelerated aging. Skin tone slackens, intercourse may be painful, and libido may become non-existent. Hormone replacement therapy (HRT) can reduce these symptoms, but concerns about risks are significant. Estrogen stimulates cell growth, so there is concern that HRT containing estrogen may allow tumors to develop in estrogen sensitive organs (breast and uterus). There remains a great debate as to whether the benefits of estrogens outweigh the risks.


illustration of ovaries overlaid on woman going through menopause
Benefits and Risks of Hormone Replacement Therapy
Benefits of Estrogen

Estrogen improves many health consequences of aging including osteoporosis, and bladder and vaginal tissue degeneration. Estrogen also acts on the cardiovascular system and the nervous system, although there is still controversy over risks and benefits for these effects. Ideally, we wish to limit aging without increasing the risk of cancer.

Risks of Estrogen

The initial results of the Women’s Health Initiative (WHI), which were released in 2002, indicated a greater risk to postmenopausal hormone replacement therapy (HRT) than previously thought. Many experts now believe the study was over generalized and alarmist, overemphasizing the risk of HRT while minimizing the benefits. In the interim, additional studies (including HERS I, HERS II, and ESTHER) have clarified many of the WHI findings, bringing those findings into proper perspective.

Ways to Take Hormone Therapy

HRT can be given orally or trans-dermally. There are advantages and disadvantages to each method of administration.

The liver detoxifies all substances that are absorbed through the intestinal tract. Everything that is ingested travels to the liver first, called the “first pass effect”. The liver inactivates many drugs, and this means that oral preparations have to be far more potent to achieve the same effect as medicines that are applied to the skin. Transdermal preparations bypass the liver and go directly into the blood stream. They therefore do not affect liver function and require far lower doses. Transdermal preparations provide more stable blood levels of hormone. Transdermal estradiol was shown to decrease circulating cortisol, insulin, triglycerides, and low-density cholesterol to normal values, which lowers risk of blood clots and has a beneficial metabolic effect in menopausal women. (Basurto, et al) They also appear to lower blood pressure. They don’t suppress natural testosterone levels as much as oral medications, which means improved orgasm and libido.

Oral estrogens are particularly useful for women who have localized reactions to patch adhesives or other objections to the transdermal approach. There are more oral products that combine estrogen and progesterone into a single delivery product. For women with contraindications to estrogen (history of breast cancer), low dose vaginal estrogen reverses vaginal dryness and bladder irritation with minimal absorption. Intravaginal DHEAS (which is turned into testosterone and estrogen) has recently been shown to improve vaginal dryness and painful intercourse without significant increase in blood levels of estrogen or testosterone.

HRT should be tailored to the individual. In light of the Women’s Health Initiative, there is pressure to minimize hormone doses and limit time a woman should use medication. We provide women with the smallest dose needed to get good symptom control, and known benefits of HRT. The decision of how long to take HRT is individualized for each patient.

“Bio-identical” Hormones

In the past few years, there’s been growing interest in “bioidentical” hormones, which are promoted as safer and more effective than FDA-approved hormones. There are estrogen products available through prescription that are “bio-identical” to a woman’s natural estrogen: estradiol 17-ß. The FDA tests products for purity, potency, efficacy and safety. Many claims made about the benefits of compounded “bio-identical”s are unproven since these drugs are not subject to FDA regulation. Because there is no regulatory oversight of these products, quality and consistency in dosing may be off. In 2001, the FDA randomly tested 37 products from 12 compounding pharmacies and found that nine (24%) were less potent than indicated. In contrast, only 2% of FDA-approved products failed the potency test when randomly sampled. There is very little information about side effects and patients do not have risk or safety information available. Insurance usually does not cover these unregulated compounded preparations. (Harvard Health Watch)

The term bio-identical means “chemically indistinguishable from the hormones produced in a woman’s body, namely estradiol 17-ß and progesterone. There are numerous FDA approved drugs that contain these hormones. These drugs are derived from plant sources and can be called “bio-identical”. (Files et al). Some FDA approved and regulated Bioidentical formulations are listed below.

Estradiol 17-ß:
Vaginal preparations Oral preparations Transdermal preparations
Vagifem Estrace Vivelle dot, Estraderm (patch)
Estrace vaginal cream Menest Climara (patch)
Estring Gynodiol Divigel (gel)
Femring Premarin Evamist (spray)

Bioidentical Progesterone (Prometrium) is FDA approved, and may be used vaginally or orally. It often causes sleepiness, so is taken at bedtime. Crinone is a vaginal Bioidentical Progesterone cream, but it generally used during fertility treatment or in early pregnancy. Estrone and estriol are often combined with estradiol by compounding formulas, but there is no indication that this mixture is any safer or more effective than FDA approved estrogens. Estriol is the estrogen most common in pregnant women. There are claims that Estriol reduces risk of breast cancer in women. In laboratory studies, estriol has been shown to prevent and even reverse breast tumors in rats — but there’s no evidence that it does so in women.

Libido and orgasm

After menopause, the ovaries produce testosterone at much lower levels then before menopause. Women who have had their ovaries removed lose about 50% of their testosterone production, with the remainder being produced by the adrenal glands. Testosterone is important for normal libido. When estrogen declines after menopause, the pituitary gland will still stimulate testosterone production by the ovary. If a postmenopausal woman takes estrogen replacement, the pituitary signal is reduced, which may lower natural testosterone production, and may lead to a decline in libido. Unfortunately, only limited studies of treatment of low sex drive (libido) and lack of orgasm have been done in women. Testosterone replacement for women has not been approved by the FDA. There is a single drug (Addyi) that has been approved for low sex drive (Hypoactive sexual desire disorder or HSDD), but it has significant side effects. Addyi can cause severely low blood pressure (hypotension) and loss of consciousness (syncope). These risks are increased and more severe when patients drink alcohol, so physicians must counsel patients on the risk of alcohol intake when using this medication.

Serum levels of testosterone do not correlate with women's sexual function according to large epidemiological studies. Whether a relative lack of testosterone activity underlies women's sexual dysfunction is unknown. The long-term safety of systemic testosterone with or without estrogen is unknown. Since women's sexual lives tend to endure as long as there is an active partner (Basson), improvement in sexual function and well-being is important for long term health. Making sense of studies of hormone therapy is difficult, since study populations differ and a wide range of sexual questionnaires have been used. (Lebbe). Testosterone replacement as well as administration of DHEAS (which is a precursor of estrogen and testosterone, but doesn’t raise blood levels of either) have both been shown to improve libido and sexual functioning. Neither is FDA approved for women, but compounding pharmacies can provide “bio-identical” creams for topical or intravaginal use.

Other problems that may cause symptoms of menopause

The symptoms of either hyperthyroidism or hypothyroidism, such as skin dryness, hot flashes, mood swings, depression, and weight gain, can mimic the symptoms of menopause. If patients on hormone replacement therapy continue to experience mood swings, depression, or sleep disturbances, patients are advised to have a thyroid function test. The AACE (American Academy of Clinical Endocrinology) recommends that all women older than age 40 have a TSH test, because studies have shown that 10% of these women have undiagnosed thyroid disease.

References
  1. Hormone replacement therapy with transdermal estradiol lowers insulin-cortisol and lipoproteins levels in postmenopausal women. Basurto L, Saucedo R, Ochoa R, Hernández M, Zárate A

  2. Bioidentical hormones: Help or hype? Harvard Health Watch

  3. Bioidentical Hormone Therapy. Julia A. Files, MD, Marcia G. Ko, MD, and Sandhya Pruthi, MD

  4. Testosterone therapy for reduced libido in women. Rosemary Basson

  5. Androgen Replacement Therapy in Women. Marie Lebbe; David Hughes; Nicole Reisch; Wiebke Arlt

  6. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Fernand Labrie, MD

Resources
back to top
 ^